AdipoRon negatively regulates proliferation and migration of ARPE-19 human retinal pigment epithelial cells

Peptides. 2021 Dec:146:170676. doi: 10.1016/j.peptides.2021.170676. Epub 2021 Oct 22.

Abstract

Adiponectin is an adipokine playing important roles in metabolic, inflammatory and proliferative processes. At the time of surgery for rhegmatogenous retinal detachment, an altered expression of adipokines has been associated with the development of future proliferative vitreoretinopathy (PVR); this evidence as well as the presence of adiponectin receptors in ocular tissues and cell lines suggests a role of adiponectin in the physio-pathology of ocular conditions. Here, we investigated the effects of AdipoRon, an adiponectin agonist, on ARPE-19, a human retinal pigment epithelial cell line after confirming the expression of AdipoR1, AdipoR2, T-cadherin receptors. We evaluated the effects of AdipoRon in terms of vitality, survival, and migration; furthermore, we investigated the potential effects of AdipoRon on the inflammatory state of ARPE-19 cells analysing the levels of IL-10, VEGF, MCP-1 and IL-6 cytokines. Our findings indicated that AdipoRon, in a time and dose-dependent manner, reduces cell proliferation, migration, and colony formation of ARPE-19 cells. On the contrary, AdipoRon administration does not affect the expression of the tested cytokines. In conclusion, our results indicated that AdipoRon, may constitute an endogenous inhibitor of retinal pigment epithelial cell proliferation and migration, both processes deeply involved in development of PVR. Since PVR are characterized by an aberrant growth, migration and dedifferentiation of retinal pigment epithelial cells, our data contribute to open new fields of research to develop innovative therapeutic targets. Further studies are needed to clarify the effects of AdipoRon and of other small-molecule adiponectin analogs on retinal epithelium to clarify the functional role of adiponectin.

Keywords: AdipoRon; Cell proliferation; Eye diseases; Human retinal pigment epithelial ARPE-19 cells; Pharmacological drug.

MeSH terms

  • Adiponectin / physiology*
  • Cell Line
  • Cell Movement / drug effects*
  • Cell Movement / physiology
  • Cell Proliferation / drug effects*
  • Cell Proliferation / physiology
  • Cytokines / metabolism
  • Humans
  • Piperidines / pharmacology*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / pathology*

Substances

  • ADIPOQ protein, human
  • AdipoRon
  • Adiponectin
  • Cytokines
  • Piperidines